The overall goal of Core A is to develop a unique and enhanced software engineering, IMRT planning and quality assurance infrastructure, that addresses the unique data management needs, error pathways, and logistical constraints posed by image guided adaptive radiation therapy (IGART). IGART confronts radiation oncology with new and unfamiliar demands: a high volume of imaging data drawn from many different modalities, new clinical tools such as deformable image registration which must perform reliably in a real- time automated mode, the need for real-time IMRT planning codes that deliver optimal plans with little or no intervention, and integration of complex software tools and functions drawn from the other projects and cores into an integrated structure. These functions include the comprehensive management and manipulation of multiple imaging data sets from diverse imaging modalities, IGART IMRT planning incorporating probabilistic models, maintaining a plan database, and acquiring statistics derived from the quantitative plan evaluation tools such as equivalent uniform dose (EUD), normal tissue complication probability (NTCP), tumor control probability (TCP), and biologically equivalent dose (BED) to accommodate variations in fraction size and to allow summation of brachytherapy and external beam dose distributions. Core A will provide the following functions to meet the overall goals of this PPG of which develops, investigates, optimizes, and implements a system to study the potential clinical advantages of IGART via coupled virtual clinical trials (VCTs) and clinical trials (ACTs). Core Function 1 will develop a novel layered software engineering and data management infrastructure, based upon a shared set of user-program data structures, common tools, and simulation scripting languages, that isolates software developers from the mechanics of storing and retrieving data and converting imaging studies from a variety of native formats to a common format for performing virtual clinical trials (VCTs) conducted by Projects 1-4. Core Function 2 will interface new tools as they are developed in Projects 1-4 into the software infrastructure, which will form the VCD IGART system. Core Function 3 will generate automated IMRT re-optimizations and treatment plans, and data analysis utilizing the VCU IGART system. Core Function 4 will focus on developing a comprehensive set of QA tools and techniques to facilitate the safe and efficient clinical implementation of IGART.